Background: Three out of every five prescriptions for proton pump inhibitors (PPIs) in hospitalized non-ICU patients are not guideline concordant. These stomach acid suppressing medications have been associated with a 25% increase in mortality risk and cost the US healthcare system over 11 billion dollars annually. Initially perceived to be harmless, evidence is mounting that PPI use is associated with many serious adverse effects such as Clostridium difficile infection (CDI), pneumonia, bone fractures, reduced serum magnesium, kidney disease and vitamin B12 deficiency. Professional guidelines define concordant PPI Rx as those prescribed for the recommended indications within indicated doses and discontinued when the diagnosis no longer exists for a given patient. PPIs are appropriately prescribed for conditions such as esophageal ulcers, gastric ulcers, duodenal ulcers, peptic ulcers, gastroduodenal ulcers, Barrett's esophagus and esophageal reflux. There is an urgent need to develop and test interventions to promote guideline concordant PPI prescription. Because PPIs increase the risk of CDI and the need for antibiotics to treat CDI, antibiotic stewardship principles may be applied to PPI stewardship also. Project Objectives: 1) Develop a PPI de-implementation intervention, assess its effectiveness and acceptability/feasibility of integrating it into an existing antibiotic stewardship program. 2) Evaluate the fidelity to the intervention by providers who include physicians, nurse practitioners, and physician assistants. Data generated will inform the design and conduct of a future multisite study. Project Methods: We will use the Systems Engineering Initiative for Patient Safety (SEIPS 2.0) model to develop and evaluate the intervention. The intervention will be housed in the existing antibiotic stewardship program. It will involve a medication reconciliation approach in which, using the electronic medical record, a pharmacist team member will send a PPI stewardship recommendation to the provider to discontinue PPI use or switch an alternative medication. We will make adaptations and changes to the intervention as we get feedback from the antibiotic stewardship team, providers, and patients. We will measure the proportion of patients receiving guideline concordant PPI in the pre-and post-intervention period. We will measure acceptability by post-intervention focus group interviews with stakeholders, including patients. We will assess intervention fidelity using a five component tool developed the Dane and Schneider. We will adapt the tool to assess the five components of exposure to the intervention, quality of delivery of the intervention, participant responsiveness to the intervention, intervention differentiation and adherence to the intervention. For example, we will query participants regarding the extent to which intervention components reached them (exposure), if communications to discontinue or continue PPI were effective (quality of delivery), and perceived intervention engagement (participant responsiveness). Impact: We anticipate that reducing unnecessary PPI use will have several positive outcomes, including fewer adverse effects?such as reduction in CDI for patients?and lower costs for the patient and the VHA system, as well as a reduction in the need for antibiotics as treatment for CDI (i.e., antibiotic stewardship). This work is significant because it will improve guideline-concordant care for PPI use in VA. The work proposed is innovative in that we will harness the existing antibiotic stewardship program to roll out PPI stewardship. The long-term goal is to reduce adverse effects related to non-guideline concordant PPI use, particularly CDI.